3-(3-Chloroanilino)-1-(3,5-dimethyl-1
H
-pyrazol-1-yl)propan-1-one
Aamer Saeed,aShahid Hussainaand Michael Bolteb*
aDepartment of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan, and b
Institut fu¨r Anorganische Chemie, J. W. Goethe-Universita¨t Frankfurt, Max-von-Laue-Strasse 7, 60438 Frankfurt/Main, Germany
Correspondence e-mail: aamersaeed@yahoo.com
Received 29 April 2009; accepted 30 April 2009
Key indicators: single-crystal X-ray study;T= 173 K; mean(C–C) = 0.002 A˚; Rfactor = 0.031;wRfactor = 0.086; data-to-parameter ratio = 14.1.
In the molecule of the title compound, C14H16ClN3O, the benzene and pyrazole rings are oriented at a dihedral angle of 3.50 (3). In the crystal structure, intermolecular N—H O
hydrogen bonds link the molecules into chains. A–contact between the benzene and pyrazole rings [centroid–centroid distance = 3.820 (3) A˚ ] may further stabilize the structure.
Related literature
For general background to 1,3,5-trisubstituted pyrazoles, see: Elguero & Goya (2002). The pyrazole chemotype is the structural motif of several highly potent inhibitors against coagulation factor Xa, see: Penning & Talley (1997); Eriksson & Quinlan (2006); Escolaret al.(2006). Pyrazole 3-carboxyl-ates have been identified as selective antagonist subtype 1PGE2 receptors (Akarca, 2005) and pyrazole-based mat-erials have been used as co-polymers for electroluminescent applications (Mella & Fagnoni, 1997). For the synthesis, see: Saeed & Mumtaz (2008). For bond-length data, see: Allenet al.(1987).
Experimental
Crystal data
C14H16ClN3O Mr= 277.75
a= 14.5389 (8) A˚
b= 7.8731 (6) A˚
c= 12.1411 (7) A˚
= 102.566 (5)
V= 1356.46 (15) A˚3
MoKradiation
= 0.28 mm1
T= 173 K
0.350.330.33 mm
Data collection Stoe IPDS II two-circle
diffractometer
Absorption correction: multi-scan (MULABS; Blessing, 1995)
Tmin= 0.909,Tmax= 0.914
8907 measured reflections 2528 independent reflections 2192 reflections withI> 2(I)
Rint= 0.034
Refinement
R[F2> 2(F2)] = 0.031
wR(F2) = 0.086
S= 1.06 2528 reflections 179 parameters
H atoms treated by a mixture of independent and constrained refinement
max= 0.22 e A˚
3 min=0.23 e A˚
3
Table 1
Hydrogen-bond geometry (A˚ ,).
D—H A D—H H A D A D—H A
N1—H1 O1i
0.828 (18) 2.293 (19) 3.1101 (15) 169.1 (16)
Symmetry code: (i)x;yþ1 2;zþ
1 2.
Data collection:X-AREA(Stoe & Cie, 2001); cell refinement: X-RED(Stoe & Cie, 2001); data reduction:X-RED; program(s) used to solve structure: SHELXS97(Sheldrick, 2008); program(s) used to refine structure:SHELXL97(Sheldrick, 2008); molecular graphics:
PLATON (Spek, 2009); software used to prepare material for publication:SHELXL97.
AS gratefully acknowledges a research grant from Quaid-i-Azam University, Islamabad, under the URF project No. DFNS/2009-36.
Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: HK2680).
References
Akarca, U. S. (2005).Curr. Pharm. Des.11, 1779–1784.
Allen, F. H., Kennard, O., Watson, D. G., Brammer, L., Orpen, A. G. & Taylor, R. (1987).J. Chem. Soc. Perkin Trans. 2, pp. S1–19.
Blessing, R. H. (1995).Acta Cryst.A51, 33–38.
Elguero, J. & Goya, P. (2002).Targets Heterocycl. Syst.6, 52–55. Eriksson, B. I. & Quinlan, D. J. (2006).Drugs,66, 1411–1415.
Escolar, G., Villata, J., Casals, F., Bozzo, J., Serradell, N. & Bolos, J. J. (2006).
Drugs Future,31, 484–487.
Mella, M. & Fagnoni, M. (1997).J. Photochem. Photobiol. A Chem.108, 143– 146.
Penning, T. D. & Talley, J. J. (1997).J. Med. Chem.40, 1347–1352. Saeed, A. & Mumtaz, A. (2008).Chin. Chem. Lett.19, 1305–1308. Sheldrick, G. M. (2008).Acta Cryst.A64, 112–122.
Spek, A. L. (2009).Acta Cryst.D65, 148–155.
Stoe & Cie (2001).X-AREAandX-RED. Stoe & Cie, Darmstadt, Germany.
Structure Reports
Online
supporting information
Acta Cryst. (2009). E65, o1231 [doi:10.1107/S1600536809016250]
3-(3-Chloroanilino)-1-(3,5-dimethyl-1
H
-pyrazol-1-yl)propan-1-one
Aamer Saeed, Shahid Hussain and Michael Bolte
S1. Comment
1,3,5-Trisubstituted pyrazoles are synthetic targets of paramount significance in the pharmacological industry, in view of
the fact that such a heterocyclic moiety represents the core structure of numerous drugs including the widely prescribed
Celebrex and Viagra (Elguero & Goya, 2002). Pyrazole chemotype is structural motif of several highly potent inhibitors
against coagulation factor Xa (Penning & Talley, 1997) among them Rivaroxaban (Eriksson & Quinlan, 2006) and
Apixaban (Escolar et al., 2006) were selected for clinical development for the prevention and treatment of thrombotic
diseases. Pyrazole 3-carboxylates were also identified as selective antagonist subtype 1PGE2 receptors (Akarca, 2005).
The pyrazole-based materials have been used as co-polymers for electroluminescent applications (Mella & Fagnoni,
1997). We report herein the crystal structure of the title compound.
In the molecule of the title compound (Fig 1), the bond lengths (Allen et al., 1987) and angles are within normal ranges.
Rings A (C11-C16) and B (N21/N22/C23-C25) are, of course, planar, and they are oriented at a dihedral angle of A/B =
3.50 (3)°.
In the crystal structure, intermolecular N-H···O hydrogen bonds (Table 1) link the molecules into chains (Fig. 2), in
which they may be effective in the stabilization of the structure. The π–π contact between the phenyl ring and the
pyrazole ring, Cg1—Cg2i [symmetry code: (i) 1 - x, 1 - y, -z, where Cg1 and Cg2 are centroids of the rings A (C11-C16)
and B (N21/N22/C23-C25), respectively] may further stabilize the structure, with centroid-centroid distance of 3.820 (3)
Å.
S2. Experimental
The title compound was prepared by cyclocondensation of pentane-2,4-dione with corresponding
3-(3-Chlorophenyl-amino) propionohydrazide according to a method reported earlier (Saeed & Mumtaz, 2008). Recrystallization from
methanol afforded the title compound (yield; 81%). Anal. calcd. for C14H16ClN3O: C, 60.54; H, 5.81; N, 15.13%; found:
C, 60.51; H, 5.83; N, 15.07%.
S3. Refinement
H atom of NH group was located in difference Fourier map and refined isotropically. The remaining H atoms were
positioned geometrically with C-H = 0.95, 0.99 and 0.98 Å, for aromatic, methylene and methyl H atoms, respectively,
and constrained to ride on their parent atoms, with Uiso(H) = xUeq(C), where x = 1.5 for methyl H and x = 1.2 for all other
Figure 1
The molecular structure of the title molecule, with the atom-numbering scheme. Displacement ellipsoids are drawn at the
Figure 2
A partial packing diagram of the title compound. Hydrogen bonds are shown as dashed lines.
3-(3-Chloroanilino)-1-(3,5-dimethyl-1H-pyrazol-1-yl)propan-1-one
Crystal data
C14H16ClN3O
Mr = 277.75
Monoclinic, P21/c
Hall symbol: -P 2ybc
a = 14.5389 (8) Å
b = 7.8731 (6) Å
c = 12.1411 (7) Å
β = 102.566 (5)°
V = 1356.46 (15) Å3
Z = 4
F(000) = 584
Dx = 1.360 Mg m−3
Mo Kα radiation, λ = 0.71073 Å
Cell parameters from 8296 reflections
θ = 3.5–25.9°
µ = 0.28 mm−1
T = 173 K
Block, orange
0.35 × 0.33 × 0.33 mm
Data collection
Stoe IPDS II two-circle diffractometer
Radiation source: fine-focus sealed tube Graphite monochromator
ω scans
Absorption correction: multi-scan (MULABS; Blessing, 1995)
2528 independent reflections 2192 reflections with I > 2σ(I)
Rint = 0.034
h = −17→16
k = −9→8
l = −14→14
Refinement
Refinement on F2
Least-squares matrix: full
R[F2 > 2σ(F2)] = 0.031
wR(F2) = 0.086
S = 1.06
2528 reflections 179 parameters 0 restraints
Primary atom site location: structure-invariant direct methods
Secondary atom site location: difference Fourier map
Hydrogen site location: inferred from neighbouring sites
H atoms treated by a mixture of independent and constrained refinement
w = 1/[σ2(F
o2) + (0.0525P)2 + 0.155P]
where P = (Fo2 + 2Fc2)/3 (Δ/σ)max < 0.001
Δρmax = 0.22 e Å−3 Δρmin = −0.23 e Å−3
Extinction correction: SHELXL97 (Sheldrick,
2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Extinction coefficient: 0.0118 (15)
Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2,
conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used
only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2
are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
x y z Uiso*/Ueq
Cl1 0.09245 (2) 0.19275 (5) 0.40578 (3) 0.03790 (14)
O1 0.56854 (7) 0.37061 (15) 0.32982 (8) 0.0338 (3)
N1 0.44533 (8) 0.16939 (17) 0.58746 (10) 0.0303 (3)
H1 0.4841 (13) 0.165 (2) 0.6485 (15) 0.035 (4)*
C1 0.47221 (8) 0.24939 (17) 0.49191 (10) 0.0230 (3)
H1A 0.4458 0.3656 0.4810 0.028*
H1B 0.4478 0.1831 0.4224 0.028*
C2 0.57897 (9) 0.25608 (17) 0.51596 (10) 0.0224 (3)
H2A 0.6019 0.3236 0.5853 0.027*
H2B 0.6041 0.1394 0.5304 0.027*
C3 0.61688 (9) 0.33260 (16) 0.42090 (10) 0.0218 (3)
C11 0.35323 (9) 0.13937 (17) 0.59318 (10) 0.0224 (3)
C12 0.27731 (9) 0.18284 (17) 0.50608 (10) 0.0232 (3)
H12 0.2873 0.2407 0.4410 0.028*
C13 0.18671 (9) 0.13994 (18) 0.51620 (11) 0.0261 (3)
C14 0.16813 (10) 0.0571 (2) 0.60922 (12) 0.0319 (3)
H14 0.1056 0.0281 0.6135 0.038*
C15 0.24443 (10) 0.01754 (19) 0.69646 (12) 0.0321 (3)
C16 0.33520 (10) 0.05718 (18) 0.68943 (11) 0.0270 (3)
H16 0.3862 0.0289 0.7500 0.032*
N21 0.71440 (8) 0.35624 (14) 0.44523 (8) 0.0211 (2)
N22 0.76632 (8) 0.30431 (14) 0.54929 (9) 0.0234 (2)
C23 0.85436 (9) 0.33838 (17) 0.54618 (11) 0.0252 (3)
C24 0.86089 (9) 0.41270 (18) 0.44162 (11) 0.0261 (3)
H24 0.9170 0.4479 0.4201 0.031*
C25 0.77205 (9) 0.42387 (16) 0.37845 (10) 0.0228 (3)
C26 0.93179 (10) 0.3031 (2) 0.64623 (13) 0.0374 (4)
H26A 0.9551 0.4104 0.6828 0.056*
H26B 0.9833 0.2441 0.6219 0.056*
H26C 0.9078 0.2315 0.6998 0.056*
C27 0.73737 (10) 0.49322 (19) 0.26314 (11) 0.0310 (3)
H27A 0.7888 0.5528 0.2390 0.046*
H27B 0.6855 0.5726 0.2636 0.046*
H27C 0.7149 0.3999 0.2107 0.046*
Atomic displacement parameters (Å2)
U11 U22 U33 U12 U13 U23
Cl1 0.01956 (19) 0.0532 (3) 0.0377 (2) 0.00375 (15) −0.00099 (14) −0.00656 (16)
O1 0.0241 (5) 0.0519 (7) 0.0233 (5) −0.0005 (5) 0.0006 (4) 0.0057 (4)
N1 0.0177 (6) 0.0487 (8) 0.0228 (6) −0.0042 (5) 0.0009 (5) 0.0071 (5)
C1 0.0182 (6) 0.0276 (7) 0.0228 (6) −0.0011 (5) 0.0033 (5) 0.0014 (5)
C2 0.0181 (6) 0.0255 (7) 0.0227 (6) −0.0010 (5) 0.0029 (5) 0.0007 (5)
C3 0.0197 (6) 0.0242 (7) 0.0209 (6) 0.0003 (5) 0.0030 (5) −0.0023 (5)
C11 0.0203 (6) 0.0229 (6) 0.0243 (6) −0.0023 (5) 0.0056 (5) −0.0041 (5)
C12 0.0211 (6) 0.0259 (7) 0.0229 (6) −0.0003 (5) 0.0055 (5) −0.0026 (5)
C13 0.0194 (6) 0.0290 (7) 0.0292 (6) 0.0005 (5) 0.0038 (5) −0.0078 (5)
C14 0.0234 (7) 0.0352 (8) 0.0401 (8) −0.0051 (6) 0.0135 (6) −0.0043 (6)
C15 0.0331 (8) 0.0337 (8) 0.0328 (7) −0.0028 (6) 0.0145 (6) 0.0030 (6)
C16 0.0274 (7) 0.0286 (7) 0.0250 (6) −0.0010 (6) 0.0058 (5) 0.0015 (5)
N21 0.0197 (5) 0.0255 (6) 0.0183 (5) −0.0011 (4) 0.0044 (4) 0.0000 (4)
N22 0.0195 (5) 0.0299 (6) 0.0199 (5) 0.0003 (5) 0.0021 (4) 0.0019 (4)
C23 0.0193 (6) 0.0296 (7) 0.0263 (6) 0.0005 (5) 0.0042 (5) −0.0025 (5)
C24 0.0222 (6) 0.0303 (7) 0.0279 (7) −0.0047 (6) 0.0102 (5) −0.0028 (5)
C25 0.0261 (6) 0.0215 (6) 0.0231 (6) −0.0031 (5) 0.0104 (5) −0.0032 (5)
C26 0.0199 (7) 0.0555 (10) 0.0345 (8) 0.0007 (7) 0.0012 (6) 0.0059 (7)
C27 0.0347 (7) 0.0370 (8) 0.0226 (6) −0.0034 (6) 0.0090 (6) 0.0028 (6)
Geometric parameters (Å, º)
Cl1—C13 1.7461 (14) C14—H14 0.9500
O1—C3 1.2116 (16) C15—C16 1.3767 (19)
N1—C11 1.3762 (17) C15—H15 0.9500
N1—C1 1.4466 (16) C16—H16 0.9500
N1—H1 0.828 (18) N21—N22 1.3850 (15)
C1—H1B 0.9900 C23—C24 1.4197 (18)
C2—C3 1.5085 (17) C23—C26 1.4916 (19)
C2—H2A 0.9900 C24—C25 1.3540 (19)
C2—H2B 0.9900 C24—H24 0.9500
C3—N21 1.3964 (17) C25—C27 1.4850 (18)
C11—C12 1.3950 (18) C26—H26A 0.9800
C11—C16 1.4093 (18) C26—H26B 0.9800
C12—C13 1.3909 (19) C26—H26C 0.9800
C12—H12 0.9500 C27—H27A 0.9800
C13—C14 1.381 (2) C27—H27B 0.9800
C14—C15 1.392 (2) C27—H27C 0.9800
C11—N1—C1 123.43 (12) C16—C15—H15 119.4
C11—N1—H1 115.4 (12) C14—C15—H15 119.4
C1—N1—H1 119.0 (12) C15—C16—C11 120.61 (13)
N1—C1—C2 107.73 (10) C15—C16—H16 119.7
N1—C1—H1A 110.2 C11—C16—H16 119.7
C2—C1—H1A 110.2 N22—N21—C25 111.49 (10)
N1—C1—H1B 110.2 N22—N21—C3 118.72 (10)
C2—C1—H1B 110.2 C25—N21—C3 129.78 (11)
H1A—C1—H1B 108.5 C23—N22—N21 104.72 (10)
C3—C2—C1 113.30 (10) N22—C23—C24 111.36 (11)
C3—C2—H2A 108.9 N22—C23—C26 120.32 (12)
C1—C2—H2A 108.9 C24—C23—C26 128.29 (12)
C3—C2—H2B 108.9 C25—C24—C23 106.98 (11)
C1—C2—H2B 108.9 C25—C24—H24 126.5
H2A—C2—H2B 107.7 C23—C24—H24 126.5
O1—C3—N21 121.39 (11) C24—C25—N21 105.44 (11)
O1—C3—C2 124.12 (12) C24—C25—C27 130.10 (12)
N21—C3—C2 114.49 (10) N21—C25—C27 124.45 (12)
N1—C11—C12 122.53 (12) C23—C26—H26A 109.5
N1—C11—C16 118.64 (12) C23—C26—H26B 109.5
C12—C11—C16 118.81 (12) H26A—C26—H26B 109.5
C13—C12—C11 118.80 (12) C23—C26—H26C 109.5
C13—C12—H12 120.6 H26A—C26—H26C 109.5
C11—C12—H12 120.6 H26B—C26—H26C 109.5
C14—C13—C12 122.99 (13) C25—C27—H27A 109.5
C14—C13—Cl1 118.68 (11) C25—C27—H27B 109.5
C12—C13—Cl1 118.33 (11) H27A—C27—H27B 109.5
C13—C14—C15 117.55 (13) C25—C27—H27C 109.5
C13—C14—H14 121.2 H27A—C27—H27C 109.5
C15—C14—H14 121.2 H27B—C27—H27C 109.5
C16—C15—C14 121.21 (13)
C11—N1—C1—C2 −178.65 (12) O1—C3—N21—N22 −177.55 (12)
N1—C1—C2—C3 178.34 (11) C2—C3—N21—N22 1.99 (16)
C1—C2—C3—N21 173.80 (11) C2—C3—N21—C25 −179.47 (12)
C1—N1—C11—C12 0.5 (2) C25—N21—N22—C23 −0.40 (14)
C1—N1—C11—C16 178.65 (13) C3—N21—N22—C23 178.39 (11)
N1—C11—C12—C13 176.66 (12) N21—N22—C23—C24 0.26 (15)
C16—C11—C12—C13 −1.49 (19) N21—N22—C23—C26 178.52 (12)
C11—C12—C13—C14 0.5 (2) N22—C23—C24—C25 −0.02 (16)
C11—C12—C13—Cl1 −179.22 (10) C26—C23—C24—C25 −178.12 (14)
C12—C13—C14—C15 0.7 (2) C23—C24—C25—N21 −0.22 (14)
Cl1—C13—C14—C15 −179.52 (11) C23—C24—C25—C27 179.06 (13)
C13—C14—C15—C16 −1.0 (2) N22—N21—C25—C24 0.39 (14)
C14—C15—C16—C11 0.0 (2) C3—N21—C25—C24 −178.23 (12)
N1—C11—C16—C15 −176.98 (13) N22—N21—C25—C27 −178.94 (12)
C12—C11—C16—C15 1.2 (2) C3—N21—C25—C27 2.4 (2)
Hydrogen-bond geometry (Å, º)
D—H···A D—H H···A D···A D—H···A
N1—H1···O1i 0.828 (18) 2.293 (19) 3.1101 (15) 169.1 (16)
